5-amino salicylic acid (5-ASA) has previously been produced from, for instance, 3-nitrobenzoic acid which is partially reduced to the corresponding hydroxylamine, which is converted in an acidic environment to 5-ASA (Ref. 1 and 2). However, the difficulties involved in purifying thus produced 5-ASA of undesired isomers restricts the usability of the method for producing pharmaceutical qualities.
Attempts have also been made in this art to produce 5-ASA by nitration of salicylic acid, but in such a method, considerable amounts of 3-isomers are obtained, which drastically reduces product yield and results in an impure end product (Ref. 3).
A further method of producing 5-ASA by reaction of carbon dioxide with p-aminophenol under high pressure, a so-called Kolbe reaction is described in the literature in this art (Ref. 4). However, this method requires access to high pressure equipment, and, furthermore, the toxicity of the p-aminophenol restricts the usability of this method from purely practical points of view.
Finally, it is previously known in the art that 5-ASA may also be produced by direct amination of salicylic acid by diazonium linking and splitting of the thus formed azo compounds. This method has also been employed in production of 5-ASA on an industrial scale. In such production, aniline (Ref. 5) is normally employed as the source of the diazonium salt, thus the use of sulphanilic acid is also described in the literature in the art (Ref. 6). For splitting of the azo bonds, use has been made of dithionite or any analogous sulphur compound which has been added in such excessive amount that this has entailed a considerable hazard to the immediate environment in the industrial production of 5-ASA. According to a recently published method (Ref. 7) the azo compound obtained according to the above method may also be split electro-chemically in a basic environment. However, this method can only be used by manufacturers who have access to the highly specialized equipment required for industrial electro-chemical synthesis.
It follows that all of the above-described methods for the production of 5-ASA suffer from manifest shortcomings either in the form of high contents of undesirable isomers in the end product paired with low product yield, or in the form of stringent requirements in respect to the handling of environmentally hazardous chemicals, or alternatively the need of expensive and complex specialized equipment.